Bispecific Antibodies in FL: EHA 2026 Explores Advancing Outcomes

Follicular lymphoma, an indolent non-Hodgkin lymphoma, is characterized by a relapsing and remitting course. While initial therapies often achieve high response rates, the disease is generally incurable, and patients frequently require subsequent lines of treatment.¹ The cumulative toxicity of multiple regimens and the development of resistance mechanisms necessitate the continuous exploration of new therapeutic strategies. Bispecific antibodies, which simultaneously engage CD3 on T-cells and a tumor-associated antigen (e.g., CD20 or CD19) on lymphoma cells, represent a significant advancement in this context.² These agents redirect T-cells to lyse malignant B-cells, offering a chemotherapy-free option with a distinct mechanism of action.³

The EHA 2026 session focused on a case-based approach to illustrate the practical application of bispecific antibodies in various clinical scenarios within FL. This format allowed for a detailed examination of patient selection, management of potential toxicities, and sequencing considerations. The discussion highlighted the importance of understanding the patient's prior treatment history, including exposure to rituximab, alkylating agents, and PI3K inhibitors, as these factors can influence the efficacy and safety profile of subsequent therapies.⁴ Follicular lymphoma is the second most common type of non-Hodgkin lymphoma, accounting for approximately 20-30% of all cases. Its incidence increases with age, with a median age at diagnosis typically in the sixth decade of life. The disease often presents with widespread lymphadenopathy and can involve the bone marrow, spleen, and other extranodal sites. The indolent nature of FL means that some patients may be managed with a "watch and wait" approach, particularly in asymptomatic early stages. However, progression or symptomatic disease necessitates active treatment, which has evolved significantly over the past decades from chemotherapy to chemoimmunotherapy and now to targeted agents. The relapsing nature of FL underscores the need for therapies that can maintain disease control and improve quality of life over extended periods.¹

What the session covered

The interactive cases presented at EHA 2026 explored the integration of currently approved and emerging bispecific antibodies for FL. Key agents discussed included mosunetuzumab and glofitamab, both targeting CD20 and CD3. Mosunetuzumab, administered as a fixed-duration intravenous regimen, has demonstrated durable responses in patients with relapsed/refractory FL. In a pivotal phase 2 study (NCT02500498), mosunetuzumab achieved a complete response (CR) rate of 60% (95% CI, 49-70) in patients who had received at least two prior lines of therapy.⁵ The median duration of response was 22.8 months. Glofitamab, also a CD20xCD3 bispecific antibody, has shown similar efficacy, with a CR rate of 68.8% (95% CI, 56.9-79.0) in a phase 2 study (NCT03075696) involving patients with heavily pretreated relapsed/refractory FL.⁶ Both agents are associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), requiring careful monitoring and management.^5,6

The session emphasized the importance of patient characteristics, such as age, comorbidities, and performance status, in determining suitability for bispecific antibody therapy. For instance, patients with a high tumor burden may experience a higher incidence or severity of CRS, necessitating proactive management strategies.⁷ The discussion also touched upon the sequencing of bispecific antibodies relative to other novel agents, such as CAR T-cell therapy. While CAR T-cells offer deep and durable responses, their logistical complexities and potential for severe toxicities may position bispecific antibodies as an earlier, more accessible option for some patients.⁸ The session did not present new trial data but rather synthesized existing evidence through a practical, case-based lens, allowing clinicians to apply the information directly to patient care scenarios. The absence of head-to-head trials comparing different bispecific antibodies or bispecific antibodies with CAR T-cell therapy means that treatment decisions currently rely on indirect comparisons and expert consensus.⁹ The session also explored the potential for resistance mechanisms to bispecific antibodies, similar to those observed with other targeted therapies. These may include antigen escape, impaired T-cell function, or alterations in the tumor microenvironment. Future research will likely focus on strategies to overcome these challenges, such as combination therapies or novel bispecific antibody designs. The discussion acknowledged that while bispecific antibodies offer a promising avenue, their optimal integration into the evolving treatment landscape for FL requires ongoing investigation and real-world data collection. The long-term safety and efficacy profiles, particularly in diverse patient populations and across multiple lines of therapy, remain areas of active study.⁹